Abstract

Aim

Brain metastases, seen in ∼30–50% of NSCLC pts, are associated with poor prognosis. ALK+ NSCLC is sensitive to the ALK inhibitor (ALKi) crizotinib, but resistance invariably occurs, often with progression in new or existing brain metastases. Ceritinib (LDK378), a novel ALKi, is highly active in pts with ALK+ NSCLC and has demonstrated central nervous system activity. Here we report efficacy and safety of ceritinib therapy in the subset of ALK+ NSCLC pts with brain metastases treated in the phase I ASCEND-1 study.

Methods

Safety and efficacy of ceritinib 750 mg/day was analyzed based on investigator assessment of adult pts with advanced ALK+ NSCLC and with clinically and neurologically stable brain metastases at study entry.

Results

Of 246 ALK+ NSCLC pts at 750 mg/day, 124 had brain metastases at study entry; 98 had ALKi pretreatment and 26 were ALKi treatment naïve. Pts with brain metastases had a median age of 51.0 years; 85.5% had an ECOG performance status of ≤1. Most pts were either Caucasian (58.1%) or Asian (39.5%); median time from initial NSCLC diagnosis to first ceritinib dose was 20.5 months. Median duration of exposure to ceritinib was 27 weeks. Efficacy is shown below.